Th17 cell and inflammatory cytokines (IL-17A, IL-17F and the like) produced thereby cause a decrease in QOL as a severe etiology cell and factor accompanying enhancement of a systemic new immune response, in various autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis, multiple sclerosis and psoriasis. However, the existing therapeutic drugs show only limited effects, and therefore, the earliest possible development of a novel therapeutic drug has been desired.
Involvement of T cells, inter alia, Th17 cell and inflammatory cytokines (IL-17A, IL-17F and the like) produced thereby, in the pathology of these immune diseases has been drawing attention in recent years.
Moreover, it has been recently clarified that a Retinoid-related Orphan Receptor (ROR) γt, which is one of the orphan nuclear receptors, plays an important role in the differentiation of Th17 cells and production of IL-17A/IL-17F. That is, it has been reported that RORγt is mainly expressed in Th17 cells and functions as a transcription factor of IL-17A and IL-17F, as well as a master regulator of Th17 cell differentiation.
Therefore, a medicament that inhibits the action of RORγt is expected to show a treatment effect on various immune diseases by suppressing differentiation and activation of Th17 cells.
WO 2002/064572A1 (patent document 1) discloses the following compound
wherein each symbol is as defined in the document, as a compound having MMP-13 inhibitory activity and effective for irritable bowel syndrome (IBS), psoriasis, multiple sclerosis and the like.
WO 2013/042782A1 (patent document 2) discloses the following compound.
wherein each symbol is as defined in the document, as a compound having RORγt inhibitory activity and effective for inflammatory bowel disease (IBD) and the like.
WO 2013/018695A1 (patent document 3) discloses the following compound
wherein each symbol is as defined in the document, as a compound having RORγt inhibitory activity and effective for inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, psoriasis and the like.
WO 2013/100027A1 (patent document 4) discloses the following compound
wherein each symbol is as defined in the document, as a compound having RORγt inhibitory activity and effective for inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, psoriasis and the like.